Ko-Dalneva, 30 pcs., 5 mg+0.625 mg+2 mg, tablets
Amlodipine
Concomitant use is not recommended
Dantrolene (intravenous administration).
In laboratory animals, cases of ventricular fibrillation with death and collapse have been reported during the use of verapamil and intravenous administration of dantrolene, accompanied by hyperkalemia. Due to the risk of hyperkalemia, it is recommended to avoid the simultaneous use of a CCB (amlodipine) and dantrolene in patients susceptible to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.
Concomitant use requiring special attention
Inducers of the CYP3A4 isoenzyme.
There are no data regarding the effect of inducers of the CYP3A4 isoenzyme on amlodipine. The simultaneous use of inducers of the CYP3A4 isoenzyme (rifampicin, St. John's wort preparations) may lead to a decrease in the concentration of amlodipine in the blood plasma. Caution should be exercised when taking amlodipine simultaneously with inducers of the CYP3A4 isoenzyme.
Inhibitors of the CYP3A4 isoenzyme.
Concomitant use of amlodipine with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungals, macrolides, such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients, and therefore monitoring of the clinical condition and dose adjustment may be required.
Concomitant use requiring attention
Amlodipine enhances the antihypertensive effect of drugs for antihypertensive therapy.
Other drug combinations.
In clinical drug interaction studies, amlodipine had no effect on the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine. Concomitant use of amlodipine and consumption of grapefruits or grapefruit juice is not recommended due to the possible increase in the bioavailability of amlodipine in some patients, which may lead to an enhanced antihypertensive effect.
Indapamide
Concomitant use requiring special attention
Drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type.
Given the risk of developing hypokalemia, caution should be exercised when using indapamide simultaneously with drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type, for example, antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol), some antipsychotics ( chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide), other drugs such as bepridil, cisapride, difemanil methyl sulfate, erythromycin IV c, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine IV, methadone, astemizole, terfenadine. Simultaneous use with the above drugs should be avoided; if hypokalemia develops, correct it and monitor the ECG (QT interval).
Drugs that can cause hypokalemia.
Concomitant use with intravenous amphotericin B, systemic corticosteroids and mineralocorticosteroids, tetracosactide, laxatives that stimulate gastrointestinal motility increases the risk of hypokalemia (additive effect). It is necessary to monitor the potassium content in the blood plasma and, if necessary, correct hypokalemia. Particular caution should be observed when used simultaneously with cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.
Cardiac glycosides.
Hypokalemia enhances the toxic effect of cardiac glycosides. With simultaneous use, you should monitor the potassium content in the blood plasma and ECG indicators and, if necessary, decide on the advisability of continuing therapy.
Concomitant use requiring attention
Metformin.
Functional renal failure, which can occur while taking diuretics, especially loop diuretics, with simultaneous use of metformin increases the risk of developing lactic acidosis. Metformin should not be used if plasma creatinine Cl exceeds 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.
Iodinated contrast agents.
Dehydration while taking diuretics increases the risk of developing acute renal failure, especially when high doses of iodinated contrast agents are administered. Before using iodinated contrast agents, it is necessary to compensate for hypovolemia.
Calcium salts.
With simultaneous use, the development of hypercalcemia may occur due to a decrease in calcium excretion by the kidneys.
Cyclosporine.
It is possible to increase Cl creatinine in blood plasma without changing the concentration of cyclosporine, even with normal water and sodium content.
Perindopril
Concomitant use is not recommended
Aliskiren.
Concomitant use of perindopril with aliskiren is contraindicated in patients with diabetes or moderate to severe renal impairment (creatinine clearance less than 60 ml/min).
Potassium-sparing diuretics, potassium supplements and potassium-containing table salt substitutes.
During therapy with ACE inhibitors, the potassium content in the blood plasma, as a rule, remains within normal limits, but hyperkalemia may develop. Concomitant use of potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood plasma. If it is necessary to take an ACE inhibitor simultaneously with the above drugs (in case of hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be carried out.
Estramustine.
The simultaneous use of ACE inhibitors with estramustine is accompanied by a risk of developing angioedema.
Concomitant use requiring special attention
Double blockade of the RAAS in patients with atherosclerosis, CHF or diabetes mellitus accompanied by target organ damage is associated with a higher incidence of arterial hypotension, fainting, hyperkalemia and renal dysfunction (including the development of acute renal failure) compared with the use of the drug one of the listed groups. Double blockade of the RAAS is possible only in selected cases under careful monitoring of renal function.
NSAIDs, including high doses of acetylsalicylic acid (ASA) (more than 3 g/day).
The simultaneous use of ACE inhibitors with NSAIDs (including ASA at a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect, as well as to a deterioration in renal function, including the development of acute renal failure, and an increase in plasma potassium levels blood, especially in patients with reduced renal function. Caution should be exercised when using this combination, especially in elderly patients. Patients need to compensate for fluid loss and regularly monitor kidney function, both at the beginning of treatment and during treatment.
Hypoglycemic agents (sulfonylureas and insulin)
ACE inhibitors may enhance the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. The development of hypoglycemia is very rare (probably due to increased glucose tolerance and decreased insulin requirements).
Concomitant use requiring attention
Diuretics (thiazide and loop).
In patients receiving diuretics, especially those with excessive fluid and/or electrolyte excretion, a significant decrease in blood pressure may be observed when initiating ACE inhibitor therapy. The risk of developing arterial hypotension can be reduced by discontinuing the diuretic, correcting hypovolemia and electrolyte balance, as well as prescribing perindopril in a low dose (2 mg/day), gradually increasing it.
Allopurinol, cytostatic and immunosuppressive drugs, GCS (for systemic use) and procainamide.
Concomitant use with ACE inhibitors may increase the risk of developing leukopenia.
Preparations for general anesthesia.
The simultaneous use of ACE inhibitors and general anesthesia may lead to increased antihypertensive effect.
Gold preparations.
When using ACE inhibitors, incl. perindopril, in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described, including facial flushing, nausea, vomiting, and arterial hypotension.
Sympathomimetics.
May weaken the antihypertensive effect of ACE inhibitors.
Gliptins (linagliptin, saxagliptin, sitagliptin, vitagliptin).
Concomitant use with ACE inhibitors may increase the risk of developing angioedema due to the inhibition of dipeptidyl peptidase IV (DPP-IV) activity by gliptin.
Ko-Dalneva®
Concomitant use is not recommended
Lithium preparations.
With the simultaneous use of ACE inhibitors with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma may occur with the development of intoxication. Concomitant use with thiazide diuretics may further increase lithium concentrations and increase the risk of intoxication. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of this therapy, regular monitoring of the concentration of lithium in the blood plasma is necessary.
Concomitant use requiring special attention
Baclofen.
The antihypertensive effect may be enhanced. Blood pressure and renal function should be monitored and, if necessary, the dose of antihypertensive drugs should be adjusted.
Concomitant use requiring attention
Antihypertensives (eg beta-blockers) and vasodilators.
When used simultaneously with antihypertensive drugs, the antihypertensive effect may be enhanced. Caution should be exercised when used concomitantly with nitroglycerin, other nitrates or other vasodilators, since an additional decrease in blood pressure may occur.
Corticosteroids (mineral and glucocorticosteroids), tetracosactide.
Decreased antihypertensive effect (fluid and sodium retention as a result of the action of corticosteroids).
Alpha blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin).
Strengthening the antihypertensive effect and increasing the risk of developing orthostatic hypotension.
Amifostine.
The antihypertensive effect of amlodipine may be enhanced.
Tricyclic antidepressants/neuroleptics/general anesthesia.
Strengthening the antihypertensive effect and increasing the risk of developing orthostatic hypotension (additive effect).
Co-dalneva tablets 10+2.5+8 mg 90 pcs. in Moscow
Ko-Dalneva®
Renal dysfunction
Co-Dalneva® is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min).
The drug Co-Dalneva® can be used in patients with moderate renal impairment (creatinine clearance 30-60 ml/min). For such patients, individual selection of doses of amlodipine, indapamide, and perindopril is recommended.
In some patients with hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment with the drug should be stopped. In the future, combination therapy can be resumed using low doses of a combination of perindopril and indapamide, or these drugs can be used separately. Such patients require regular monitoring of potassium levels and creatinine concentrations in the blood serum 2 weeks after the start of therapy and every 2 months thereafter.
In patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood serum, which usually resolves when therapy is discontinued.
The development of renal failure more often occurs in patients with severe CHF or underlying renal impairment, including renal artery stenosis.
Arterial hypotension and water-electrolyte imbalance
Patients with hyponatremia (especially with renal artery stenosis, including bilateral) are at risk of sudden development of arterial hypotension. Therefore, you should pay attention to possible symptoms of dehydration and decreased electrolyte levels in the blood plasma, for example, after diarrhea or vomiting. The use of ACE inhibitors causes blockade of the RAAS, and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma, which indicates the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy and sometimes develop acutely. Such patients require regular monitoring of blood plasma electrolyte levels. In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required. Transient arterial hypotension is not a contraindication for continued therapy. After restoration of circulating blood volume (CBV) and blood pressure, treatment can be resumed using low doses of perindopril and indapamide, or used separately.
Elderly patients
Before starting to take Co-Dalneva®, it is necessary to evaluate the functional activity of the kidneys and the potassium content in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of decrease in blood pressure, especially in the case of a decrease in blood volume and loss of electrolytes, which helps to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of developing arterial hypotension exists in all patients, however, special caution should be observed in patients with coronary artery disease and cerebrovascular diseases. In such patients, treatment begins with low doses of the drug.
Children
The drug Co-Dalneva® is contraindicated for use in children under 18 years of age due to the lack of data on effectiveness and safety in this age group.
Amlodipine
The effectiveness and safety of amlodipine in hypertensive crisis has not been established.
Heart failure
Patients with heart failure should be treated with caution.
When using amlodipine in patients with CHF functional class III and IV according to the NYHA classification, pulmonary edema may develop. BMCCs, including amlodipine, should be used with caution in patients with CHF due to a possible increased risk of adverse events from the cardiovascular system and mortality.
Liver failure
In patients with impaired liver function, T½ and AUC of amlodipine increase. Recommendations for dosing of the drug have not been established. Amlodipine should be started with the lowest doses and precautions should be taken both at the beginning of treatment and when increasing the dose. In patients with severe hepatic impairment, the dose should be increased gradually, ensuring careful monitoring of the clinical condition.
Elderly patients
In elderly patients, increasing the dose should be done with caution (see sections “Dosage and Administration” and “Pharmacological properties. Pharmacokinetics”).
Kidney failure
Patients with renal failure can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Amlodipine is not excreted from the body by dialysis.
Mitral stenosis/aortic stenosis/HOCM
Amlodipine is contraindicated in patients with left ventricular outflow tract obstruction.
Withdrawal syndrome
Despite the absence of withdrawal syndrome in BMCC, it is advisable to discontinue treatment with Dalneva® gradually, reducing the dose of the drug. Amlodipine does not prevent the development of withdrawal syndrome after abrupt cessation of beta-blockers.
Peripheral edema
Mild to moderate peripheral edema was the most common adverse event of amlodipine in clinical studies. The incidence of peripheral edema increases with increasing dose (when using amlodipine at a dose of 2.5 mg, 5 mg and 10 mg per day, edema occurred in 1.8%, 3% and 10% of patients, respectively). Peripheral edema associated with the use of amlodipine should be carefully differentiated from symptoms of progression of left ventricular heart failure.
Other
It is necessary to maintain dental hygiene and follow-up with a dentist (to prevent pain, bleeding and gum hyperplasia).
Perindopril
Hypersensitivity/angioedema (Quincke's edema)
When using ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, lips, tongue, vocal folds and/or larynx may occur. This can happen at any time. If these symptoms appear, use of Dalneva® should be stopped immediately, and the patient should be observed until signs of edema disappear completely. If angioedema affects only the face and lips, its manifestations usually go away on their own, or antihistamines can be used to treat its symptoms drugs. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death. If such symptoms appear, epinephrine (adrenaline) at a dilution of 1:1000 (0.3 or 0.5 ml) should be immediately administered subcutaneously and/or provide airway patency. The patient should be under medical supervision until symptoms disappear completely and permanently.
Patients with a history of angioedema not associated with the use of ACE inhibitors may have an increased risk of developing it when using drugs of this group (see section “Contraindications”).
In rare cases, intestinal angioedema (angioedema of the intestine) develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal serum concentrations of C1-esterase. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping the use of ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when making a differential diagnosis, it is necessary to take into account the possibility of developing intestinal angioedema (see section “Side effects”).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (eg, temsirolimus, everolimus, sirolimus) or DPP-IV (gliptins, including vildagliptin) increases the risk of developing angioedema (eg, swelling of the upper airway or tongue, with or without respiratory dysfunction ) (see section “Interaction with other drugs”).
Caution should be exercised when initiating therapy with racecadotril, mTOR inhibitors (eg, temsirolimus, everolimus, sirolimus) or gliptins, including vildagliptin, when used concomitantly with ACE inhibitors.
Anaphylactoid reactions during desensitization procedures
There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy with hymenoptera venom. In these same patients, an anaphylactoid reaction was avoided by temporarily discontinuing ACE inhibitors, and if the drug was accidentally taken, the anaphylactoid reaction occurred again.
Anaphylactoid reactions during LDL apheresis using dextran sulfate
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each LDL apheresis procedure using dextran sulfate.
Neutropenia/agranulocytosis, thrombocytopenia and anemia
In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. In patients with normal renal function in the absence of other aggravating factors, neutropenia rarely develops.
Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with impaired renal function.
Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Renovascular hypertension
In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, the risk of developing arterial hypotension and renal failure increases during therapy with ACE inhibitors. Taking diuretics may be an additional risk factor. Deterioration of renal function can be observed with even a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis.
Double blockade of the RAAS
There is evidence that the simultaneous use of ACE inhibitors, ARB II or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. If therapy with dual blockade of the RAAS is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, plasma electrolytes and blood pressure. The use of ACE inhibitors simultaneously with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").
Primary hyperaldosteronism
Patients with primary hyperaldosteronism are usually not susceptible to antihypertensive drugs whose action is based on inhibition of the RAAS. Therefore, taking the drug is not recommended.
Arterial hypotension
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients without concomitant diseases. The risk of a pronounced decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe hypertension with high renin activity (see sections “Interaction with other drugs" and "Side effects"). In patients at increased risk of developing symptomatic arterial hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored during treatment with Dalneva®.
A similar approach is also used in patients with angina pectoris and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.
If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, the blood volume should be replenished using intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of blood volume and blood pressure, treatment can be continued.
Mitral stenosis/aortic stenosis/HOCM
Perindopril, like other ACE inhibitors, should be prescribed with caution in patients with left ventricular outflow tract obstruction (aortic stenosis, HOCM), as well as in patients with mitral stenosis. Amlodipine is contraindicated in patients with left ventricular outflow tract obstruction.
Renal dysfunction
For patients with renal failure (creatinine clearance less than 60 ml/min), individual selection of doses of perindopril and amlodipine is recommended (see section “Dosage and Administration”). Such patients require regular monitoring of potassium levels and creatinine concentrations in the blood serum (see section “Side Effects”).
In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney during therapy with ACE inhibitors, an increase in serum urea and creatinine concentrations is possible, which usually resolves when therapy is discontinued. This effect is most often observed in patients with renal failure. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients. In some patients with hypertension without signs of renal vascular damage, an increase in serum urea and creatinine concentrations is possible, especially when perindopril is co-administered with a diuretic, usually slight and transient. This effect is more often observed in patients with pre-existing renal impairment.
Liver dysfunction
In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes in the blood plasma while taking ACE inhibitors, you should stop taking the drug (see section “Side Effects”) and consult a doctor.
Ethnic differences
In patients of the Negroid race, angioedema develops more often than in representatives of other races while using ACE inhibitors. Perindopril, like other ACE inhibitors, may have a less pronounced antihypertensive effect in patients of the Black race compared to representatives of other races. Perhaps this difference is due to the fact that patients of the Negroid race with hypertension more often have low plasma renin activity.
Cough
During therapy with an ACE inhibitor, a dry cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. This should be taken into account when carrying out the differential diagnosis of cough.
Surgery/general anesthesia
In patients undergoing major surgery and/or the use of general anesthesia that causes hypotension, the use of perindopril may block the formation of angiotensin II against the background of compensatory renin release. Treatment should be stopped one day before surgery. If arterial hypotension develops according to this mechanism, blood pressure should be maintained by replenishing blood volume.
Hyperkalemia
ACE inhibitors may cause hyperkalemia because they inhibit the release of aldosterone. This effect is usually minor in patients with normal renal function. However, in patients with impaired renal function and/or in patients concomitantly taking drugs containing potassium (including potassium-containing salt substitutes), potassium-sparing diuretics, trimethoprim or co-trimoxazole (fixed combination of trimethoprim and sulfamethoxazole), and in particular aldosterone antagonists or ARB II, hyperkalemia may develop. Risk factors for the development of hyperkalemia are renal failure, impaired renal function, age over 70 years, diabetes mellitus, intercurrent conditions (in particular, dehydration, acute decompensation of CHF, metabolic acidosis), simultaneous use of potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride ), potassium preparations or potassium-containing salt substitutes, or the simultaneous use of other drugs that increase the content of potassium in the blood plasma (for example, heparin, co-trimoxazole). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. Potassium-sparing diuretics and ARB II should be used with caution in patients receiving ACE inhibitors, and serum potassium levels and renal function should be regularly monitored (see section "Interaction with other drugs").
Patients with diabetes mellitus
When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin, during the first month of therapy it is necessary to carefully monitor the concentration of glucose in the blood (see section “Interaction with other drugs”).
The use of Dalneva® in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use.
Indapamide
In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the drug.
Photosensitivity
Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics. If a photosensitivity reaction develops, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.
Water and electrolyte balance
Sodium content in blood plasma
Before starting treatment, it is necessary to determine the sodium content in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. At the initial stage of therapy, a decrease in sodium levels in the blood plasma may be asymptomatic, so regular laboratory monitoring is necessary. Elderly patients are advised to monitor plasma sodium levels more frequently.
Hyponatremia in combination with hypovolemia can cause dehydration and orthostatic hypotension.
A concomitant decrease in chlorine content in the blood plasma can lead to secondary compensatory metabolic alkalosis (the incidence and severity of this effect are insignificant).
Potassium content in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. It is necessary to avoid hypokalemia (less than 3.4 mmol/l) in the following categories of patients from high-risk groups: elderly patients, malnourished patients, patients with liver cirrhosis, including edema and ascites, patients with coronary artery disease, CHF. In such patients, hypokalemia enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.
Patients with a prolonged QT interval, either hereditary or drug-induced, are also at increased risk. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal. In all the cases described above, regular monitoring of the potassium content in the blood plasma is necessary. It is necessary to determine the potassium content in the blood plasma during the first week after starting therapy. If hypokalemia is detected, appropriate therapy should be provided.
Calcium content in blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, which may cause a slight temporary increase in calcium levels in the blood plasma. Severe hypercalcemia may be associated with previously undiagnosed hyperparathyroidism. In such cases, it is necessary to conduct a study of the function of the parathyroid glands, having first stopped taking diuretics.
Uric acid
In patients with elevated concentrations of uric acid in the blood plasma, the frequency of gout attacks may increase during therapy.
Renal dysfunction
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adult patients below 25 mg/l or 220 µmol/l). In elderly patients, CC is calculated taking into account age, body weight and gender.
In patients with hypovolemia and hyponatremia at the beginning of diuretic therapy, a temporary decrease in GFR and an increase in the concentration of urea and creatinine in the blood plasma may be observed. This transient functional renal failure is not dangerous for patients with unchanged renal function, but its severity may increase in patients with renal failure.
In such patients, potassium levels and plasma creatinine concentrations should be regularly monitored.
Athletes
Indapamide may give a positive reaction during doping control.
Acute myopia and secondary acute angle-closure glaucoma
Sulfonamides and their derivatives can cause an idiosyncratic reaction, leading to the development of acute transient myopia and an acute attack of angle-closure glaucoma. If left untreated, an acute attack of angle-closure glaucoma can lead to permanent vision loss. First of all, it is necessary to stop taking the drug as quickly as possible. If intraocular pressure remains uncontrolled, emergency medication or surgery may be required. Risk factors for the development of an acute attack of angle-closure glaucoma are a history of allergic reactions to sulfonamide derivatives and penicillins.
Impact on driving vehicles and machinery
Due to the possibility of dizziness, drowsiness and other side effects while using the drug Dalneva®, care must be taken when driving vehicles and working with other technical devices that require increased concentration and speed of psychomotor reactions, especially at the beginning of treatment and when increasing the dose.
Dalneva, 10 mg+4 mg, tablets, 30 pcs.
Special instructions regarding amlodipine and perindopril also apply to Dalneva®.
Perindopril
Hypersensitivity/angioedema (Quincke's edema).
When using ACE inhibitors, incl. perindopril, in rare cases, the development of angioedema of the face, lips, tongue, vocal folds and/or larynx may occur. If these symptoms appear, the use of Dalneva® should be stopped immediately, and the patient should be observed until signs of edema disappear completely.
If angioedema affects only the face and lips, its symptoms usually resolve on their own, or antihistamines can be used to treat the symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.
If such symptoms appear, you should immediately administer subcutaneous epinephrine (adrenaline) at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency. The patient should be under medical supervision until symptoms disappear completely and permanently.
Patients with a history of angioedema not associated with the use of ACE inhibitors may have an increased risk of developing it when using drugs in this group.
In rare cases, intestinal angioedema (angioedema of the intestine) develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping the use of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing intestinal angioedema must be taken into account when making a differential diagnosis.
Anaphylactoid reactions during desensitization procedures.
There are isolated reports of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy with
Hymenoptera
. ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, the development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis using dextran sulfate
. In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flux membranes.
Hemodialysis.
Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.
Neutropenia/agranulocytosis, thrombocytopenia and anemia.
In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors.
Perindopril should be used with great caution in patients with connective tissue diseases who are simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing renal impairment. Some patients may develop severe infections that do not respond to intensive antibiotic therapy. If perindopril is prescribed, monitoring the number of leukocytes in the blood plasma is recommended. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.
Risk of arterial hypotension and/or renal failure (including in patients with CHF, impaired water and electrolyte balance).
In liver cirrhosis, accompanied by edema and ascites, arterial hypotension, and CHF, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a diet with limited salt or long-term use of diuretics).
The use of an ACE inhibitor causes blockade of the RAAS, and therefore a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose or during the first two weeks of therapy with Dalneva®.
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely occurs in patients without underlying medical conditions. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, while following a strict diet with limited salt, hemodialysis, diarrhea or vomiting, or in patients with severe arterial hypertension with high renin activity. In patients at high risk of developing symptomatic hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored during treatment with Dalneva®.
The same precautions apply to patients with angina pectoris or cerebrovascular diseases, in whom a pronounced decrease in blood pressure can lead to the development of myocardial infarction or cerebrovascular accident.
If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, the volume of blood volume should be replenished with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for further use of the drug Dalneva®. After restoration of blood volume and blood pressure, treatment with Dalneva® can be continued.
Aortic stenosis/mitral stenosis/hypertrophic obstructive cardiomyopathy.
ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.
Potassium-sparing diuretics and potassium supplements.
The simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes is not recommended.
Cough.
During therapy with an ACE inhibitor, a dry, nonproductive cough may occur, which disappears after discontinuation of drugs in this group. If a dry cough appears, you should be aware of the possible connection of this symptom with the use of an ACE inhibitor.
Children and teenagers under 18 years of age.
Dalneva® is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of the drug in this age group.
Renal dysfunction.
If renal function is impaired (creatinine Cl less than 60 ml/min), individual selection of doses of perindopril and amlodipine is recommended. Regular monitoring of potassium and creatinine levels in the blood plasma is a necessary condition in the treatment of such patients. In some patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney, taking ACE inhibitors, there was an increase in plasma urea and creatinine concentrations, reversible after discontinuation of therapy. These changes are more likely in patients with renal failure. Patients with renovascular hypertension are at increased risk of severe hypotension and renal failure. In some hypertensive patients without obvious evidence of existing renal disease who took perindopril concomitantly with a diuretic, small and transient increases in serum urea and creatinine concentrations were observed. These changes are more likely to develop in patients with pre-existing renal impairment.
Liver dysfunction.
Rarely, the use of ACE inhibitors is accompanied by a syndrome, the development of which begins with cholestatic jaundice and then progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice occurs or liver transaminases increase during use of an ACE inhibitor, the ACE inhibitor should be discontinued immediately and the patient should remain under appropriate medical supervision.
Ethnic characteristics.
In patients of the Negroid race, angioedema develops more often than in representatives of other races while using ACE inhibitors. Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race more often have low plasma renin activity.
Surgical interventions/general anesthesia.
The use of ACE inhibitors in patients undergoing major surgery and/or general anesthesia can lead to a significant decrease in blood pressure if general anesthesia agents with a hypotensive effect are used. This is due to blocking the formation of angiotensin II against the background of a compensatory increase in renin activity. If the development of arterial hypotension is associated with the described mechanism, the blood volume should be increased. It is recommended to stop using the drug 24 hours before surgery.
Hyperkalemia.
During therapy with ACE inhibitors, including perindopril, plasma potassium levels may increase in some patients. Risk factors for the development of hyperkalemia are renal failure, decreased renal function, old age (over 70 years), diabetes mellitus, intercurrent conditions, in particular dehydration, acute cardiac decompensation, metabolic acidosis, simultaneous use of potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride), drugs or supplements containing potassium, potassium-containing table salt substitutes, or concomitant use of other drugs that increase the level of potassium in the blood plasma (for example, heparin). Hyperkalemia can cause serious, sometimes life-threatening arrhythmias. If it is necessary to use perindopril and one of the above substances simultaneously, caution should be exercised and the potassium level in the blood plasma should be regularly monitored.
Patients with diabetes.
In patients with diabetes mellitus taking oral hypoglycemic agents and/or insulin, increased monitoring of blood glucose concentrations is necessary during the first few months of therapy with ACE inhibitors.
Amlodipine
Liver dysfunction.
In patients with impaired liver function, T1/2 of amlodipine is prolonged. When prescribing the drug to such patients, caution should be exercised and liver enzyme activity should be regularly monitored.
Patients with heart failure.
In patients with CHF (functional class III and IV according to the NYHA classification), treatment is carried out with caution due to the possibility of developing pulmonary edema.
Impact on the ability to drive vehicles and other technical devices.
Due to the possibility of dizziness and other side effects while using the drug Dalneva®, care must be taken when driving vehicles and working with other technical devices that require increased concentration and speed of psychomotor reactions.
